Certain sulfonyl carbamate on thiocarbamate intermediates

ABSTRACT

There is described a process for producing sulfonylureas of the formula ##STR1## wherein G is an unsubstituted or substituted furanyl, thienyl, pyrrolyl, pyridinyl or phenyl radical, 
     X is alkyl, haloalkyl, alkoxy, alkylthio, halogen, haloalkoxy, alkylamino or dialkylamino, 
     Y is alkyl, alkoxy or haloalkoxy, 
     Z is a nitrogen atom or the methyne group --CH═. 
     This novel process comprises reacting a sulfonamide of the formula 
     
         G--SO.sub.2 --NH.sub.2, 
    
     in the presence of a base, with a chloroformic acid ester of the formula 
     
         Cl--CO--Q--T, 
    
     or a sulfonyl chloride of the formula 
     
         G--SO.sub.2 Cl, 
    
     in the presence of a base, with a urethane of the formula 
     
         H.sub.2 N--CO--Q--T; 
    
     and converting the formed carbamate of the formula 
     
         G--SO.sub.2 --NH--CO--Q--T 
    
     by reaction with an amine of the formula ##STR2## into the sulfonylurea of the above formula. There are also described novel sulfonylcarbamates of the above formula as intermediates.

This is a divisional of application Ser. No. 511,830 filed on July 8,1983. Now U.S. Pat. No. 4,518,776.

The present invention relates to a novel process for producingsulfonylureas having a herbicidal action and an action regulating plantgrowth, and also to novel sulfonylcarbamates produced as intermediates.

The sulfonylureas to be produced by the novel process according to theinvention are described, together with their properties, in the U.S.Patent Specifications Nos. 4,127,405, 4,301,286 and 4,302,241, in theEuropean Offenlegungsschriften Nos. 23422, 44807 and 44808, and also inthe Swiss Patent Applications Nos. 4667/81-0, 5075/81-2 and 2205/82-3.

The known processes are disadvantageous either in that isocyanatederivatives or isothiocyanate derivatives have to be reacted, thehandling of which is difficult on account of the high reactivity of thisclass of compounds, or in that there occur during the synthesis fromphenyl carbamates ecologically unfavourable by-products, for examplephenols.

It is therefore the object of the present invention to provide a processwhich avoids the use of compounds difficult to handle, and theoccurrence of by-products which contaminate the environment.

It is hence suggested according to the invention that the herbicidal andplant-growth-regulating sulfonylureas of the general formula I ##STR3##wherein Z is an --N═ or --CH═radical,

G is a radical of the formula ##STR4## X is C₁ -C₄ -alkyl, C₁ -C₄-haloalkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -alkylthio, halogen, C₁ -C₄-haloalkoxy, C₁ -C₄ -alkylamino or di-C₁ -C₄ -alkylamino,

Y is C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy or C₁ -C₄ -haloalkoxy,

A is oxygen, sulfur, --NR₅ -- or --C═N--, where R₅ is hydrogen, C₁ -C₄-alkyl or --CO-C₁ -C₄ -alkyl,

R₁ is hydrogen, C₁ -C₄ -alkyl, halogen, nitro, cyano, --NH₂, --S(O)_(n)C₁ -C₄ -alkyl, --SO₂ -C₁ -C₄ -alkoxy, --SO₂ -di-C₁ -C₄ -alkylamino,--CHO, --CONH₂, --D-C₃ -C₅ -alkynyl, --CO-D-C₃ -C₅ -alkynyl, --D--C₁ -C₄-alkyl, --D-C₃ -C₅ -alkenyl, --CO-C₁ -C₄ -alkyl, --CO-D-C₁ -C₄ -alkyl or--CO-D-C₃ -C₅ -alkenyl, n being one or two, and D being an oxygen,sulfur, --NH-- or --N(C₁ -C₄ -alkyl)-bridge,

R₂ is hydrogen, halogen, CF₃, NO₂, C₁ -C₄ -alkyl or C₁ -C₄ -alkoxy,

R₃ is hydrogen, fluorine or chlorine, and

R₄ is halogen, C₁ -C₄ -alkyl, nitro, cyano, --NH₂, --S(O)_(n) -C₁ -C₄-alkyl, --SO₂ -C₁ -C₄ -alkoxy, --SO₂ -di-C₁ -C₄ -alkylamino, --CHO,--CONH₂, --D-C₃ -C₅ -alkynyl, --CO-D-C₃ -C₅ -alkynyl, trifluoromethyl,or C₁ -C₄ -alkoxy substituted by cyano, halogen, C₁ -C₄ -alkoxy or C₁-C₄ -alkylthio, or is --D-C₁ -C₄ -alkyl, --D-C₃ -C₅ -alkenyl, --CO-C₁-C₄ -alkyl, 1,2-dichlorovinyloxy, --CO-D-C₁ -C₄ -alkyl or --CO-D-C₃ -C₅-alkenyl, n being one or two, and D being an oxygen, sulfur, --NH-- or--N(C₁ -C₄ -alkyl)-bridge,

be produced by a process comprising reacting a sulfonamide of theformula II

    G--SO.sub.2 --NH.sub.2                                     (II),

in the presence of a base, with a chloroformic acid ester of the formulaIII

    Cl--CO--Q--T                                               (III),

or a sulfonyl chloride of the formula IV

    G---SO.sub.2 --Cl                                          (IV),

in the presence of a base, with a urethane of the formula V

    H.sub.2 N--CO--Q--T                                        (V)

wherein G has the meaning defined under the formula I,

Q is oxygen or sulfur, and

T is C₁ -C₄ -alkyl, benzyl, C₁ -C₄ -haloalkyl, C₁ -C₃ -cyanoalkyl, C₂-C₅ -alkenyl, or alkoxyalkyl or alkylthioalkyl having a total of at most5 carbon atoms;

and converting the formed carbamate of the formula VI

    G--SO.sub.2 --NH--CO--Q--T                                 (VI)

by reaction with an amine of the formula VII ##STR5## wherein G, Q, T,X, Y and Z have the meanings defined in the foregoing, into thesulfonylurea of the formula I.

By halogen is meant within the scope of the above definition in generalfluorine, chlorine, bromine or iodine, fluorine and chlorine beingpreferred. Preferred as substituent of the radical G is particularlychlorine, and as substituent of an alkyl group, which in its turn can bepart of a radical, especially fluorine.

Examples of alkyl are: methyl, ethyl, n-propyl and i-propyl or theisomeric butyl groups. Alkyl is itself to be understood as being asubstituent or as part of another substituent, for example alkoxy oralkylthio. Preferred alkyl groups are in each case unbranched alkylchains, especially however methyl and ethyl.

By alkenyl is meant as a rule: allyl, 2-butenyl, 3-butenyl,2-isobutenyl, isopropenyl, 2-pentenyl, 3-pentenyl or 4-pentenyl,particularly allyl and 4-pentenyl.

By alkynyl is meant in general: propargyl, 2-butynyl, 3-butynyl,methylpropargyl, 2-pentynyl, 3-pentynyl and 4-pentynyl.

The heterocycles which are embraced by the definition of the radical Gare: thiophene, furan, pyrrole and pyridine.

Preferred pyrimidine and triazine rings are those in which X is methyl,ethyl, fluoromethyl, trifluoromethyl, methoxy, ethoxy, i-propyloxy,methylthio, chlorine, bromine, difluoromethoxy, 2,2,2-trifluoroethoxy,methylamino or dimethylamino, and Y is methyl, methoxy ordifluoromethoxy.

The reaction of the sulfonamides of the formula II with the chloroformicacid esters of the formula III can be performed in the presence of asuitable inert aprotic solvent, or in the absence of a solvent. The useof a solvent has however proved advantageous. Suitable solvents are:hydrocarbons, such as benzene, toluene and xylene; ethers, such asdiethyl ether, ethylene glycol dimethyl ether, diethylene glycoldimethyl ether, tetrahydrofuran and dioxane; ketones, such as acetone,ethyl methyl ketone and cyclohexanone; nitriles, such as acetonitrileand propionitrile; and dimethyl sulfoxide. The reaction is performed inthe presence of at least equimolecular amounts of a base. Suitable basesare carbonates, such as sodium and potassium carbonate, hydrogencarbonates, such as sodium and potassium hydrogen carbonates, oxides,such as calcium and magnesium oxides, and tertiary amines, such astrimethylamine, triethylamine, quinuclidine, quinoline, pyridine andtripropylamine. The base is advantageously used in excess. There arethus preferably used 1 to 5 mols of base, especially 1.1 to 1.5 mols,per mol of sulfonamide. Larger excesses of base are used in particularwhen the reaction is performed without solvent, and the base, preferablya liquid tertiary amine, simultaneously serves as reaction medium. Thereaction temperatures are as a rule between 0° and 140° C., preferablybetween 10° and 80° C.

The reaction of the sulfonyl chlorides of the formula IV with theurethanes of the formula V is carried out under the same reactionconditions as those for the reaction of the compounds of the formulae IIand III.

The sulfonylcarbamates of the formula VI obtained as intermediates arereacted with the amines of the formula VII by the mixture of the tworeactants being heated until a cleavage of the alcohol or mercaptan hasoccurred. The reaction can be performed either without solvent or in thepresence of an inert solvent. The reaction mixture is in general heateduntil the commencement of the cleavage reaction of alcohol or mercaptan,and is held at this temperature until a complete conversion is obtained.The temperature is as a rule 50° to 220° C., preferably 80° to 160° C.Solvents which have proved suitable are: hydrocarbons, such as benzene,toluene, xylene, mesitylene, tetrahydronaphthalene, decalin, cyclohexaneand higher-boiling ligroin fractions; ethers, such as tetrahydrofuran,dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethylether and diphenyl ether; nitriles, such as acetonitrile orpropionitrile; ketones, such as ethyl methyl ketone, cyclohexanone andacetone, and dimethylsulfoxide.

In a preferred embodiment of the process according to the invention, theprocedure comprises reacting a sulfonamide of the formula II with achloroformic acid ester of the formula III, or reacting a sulfonylchloride of the formula IV, in the presence of a base and in an inertsolvent at 10° to 80° C., with a urethane; and heating the resultingcarbamate of the formula VI together with an amine of the formula VII,in an inert solvent at 80° to 160° C., until the cleavage reaction ofalcohol or mercaptan has finished; and isolating the product.

The starting compounds of the formulae II, III, IV, V and VII are known,and can be produced by known methods.

The sulfonylcarbamates of the narrower subformula VIa are novel and weredeveloped specially for carrying out the process according to theinvention. They therefore form further subject matter of the presentinvention. The novel sulfonylcarbamates correspond to the generalformula VIa

    G--SO.sub.2 --NH--CO--Q--T                                 (VIa)

wherein

Q is oxygen or sulfur,

T is C₁ -C₄ -alkyl, C₁ -C₄ -haloalkyl, C₁ -C₃ -cyanoalkyl, C_(2-C) ₅-alkenyl, benzyl, or alkoxyalkyl or alkylthioalkyl having a total of atmost 5 carbon atoms

G is a radical of the formula ##STR6## wherein A is oxygen, sulfur,--NR₅ -- or --C═N--, where R₅ is hydrogen, C₁ -C₄ -alkyl or --CO--C₁ -C₄-alkyl,

R₁ is hydrogen, C₁ -C₄ -alkyl, halogen, nitro, cyano, --NH₂, --S (O)_(n)--C₁ -C₄ -alkyl, --SO₂ --C₁ -C₄ -alkoxy, --SO₂ -di-C₁ -C₄ -alkylamino,--CHO, --CONH₂, --D-C₃ -C₅ -alkynyl, --CO-D-C₃ -C₅ -alkynyl, --D-C₁ -C₄-alkyl, --D-C₃ -C₅ -alkenyl, --CO-C₁ -C₄ -alkyl, --CO-D-C₁ -C₄ -alkyl or--CO-D-C₃ -C₅ -alkenyl, n being one or two, and D being an oxygen,sulfur, --NH-- or --N(C₁ -C₄ -alkyl)bridge,

R₂ is hydrogen, halogen, CF₃, NO₂, C₁ -C₄ -alkyl or C₁ -C₄ -alkoxy,

R₃ is hydrogen, fluorine or chlorine, and

R₄ is halogen, C₁ -C₄ -alkyl, nitro, cyano, --NH₂, --S(O)_(n) -C₁ -C₄-alkyl, --SO₂ -C₁ -C₄ -alkoxy, --SO₂ -di-C₁ -C₄ -alkylamino, --CHO,--CONH₂, --D-C₃ -C₅ -alkynyl, --CO-D-C₃ -C₅ -alkynyl, trifluoromethyl,or C₁ -C₄ -alkoxy substituted by cyano, halogen, C₁ -C₄ -alkoxy or C₁-C₄ -alkylthio, or is --D-C₁ -C₄ -alkyl, --D-C₃ -C₅ -alkenyl, --CO-C₁-C₄ -alkyl, 1,2-dichlorovinyloxy, --CO-D-C₁ -C₄ -alkyl or --CO-D-C₃ -C₅-alkenyl, n being 1 or 2, and D being an oxygen, sulfur, --NH-- or--N(C₁ -C₄ -alkyl)bridge, with the proviso that

(a) the radical --Q--T is not ethoxy or butyloxy when G is theunsubstituted 2-thienyl radical,

(b) the radical --Q--T is not methylthio when G is the 2-tolyl radical,

(c) the radical --Q--T is not ethoxy when G is the2-trifluoromethylphenyl radical or the 2-anisyl radical, and

(d) the radical --Q--T is not methoxy when G is the2-methoxycarbonylphenyl radical or the 2-ethylthiocarbonylphenylradical.

The Examples which follow serve to further illustrate the invention.

EXAMPLE 1 N-(2-Difluoromethoxyphenyl-sulfonyl)-ethoxycarbamate

1.15 g of 55% sodium hydride are added to a solution of 2.2 g ofcarbamic acid ethyl ester in 30 ml of ethylene glycol dimethyl ether at20° to 25° C. The formed suspension is stirred at 20° to 25° C. for 30minutes; it is then cooled to 10° C. and 6.0 g of2-difluoromethoxybenzenesulfonyl chloride are added dropwise. Thereaction is exothermic, and a slight evolution of gas occurs. After thereaction mixture has been stirred at 20° to 25° C. for one hour, thesolvent is evaporated off, and 50 ml of ice-water are added to theresidue. The yield after extraction with ethyl acetate, drying,concentration by evaporation of the organic phase and purification ofthe residue by column-chromatography on silica gel with methylenechloride is 1.7 g (23.3% of theory) ofN-(2-difluoromethoxyphenyl-sulfonyl)-ethylcarbamate, m.p. 111°-113° C.

EXAMPLE 2N-(2-Difluoromethoxyphenyl-sulfonyl)-N'-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)-urea

A solution of 1.48 g ofN-(2-difluoromethoxy-phenylsulfonyl)-ethylcarbamate and 0.62 g of2-amino-4-methoxy6-methyl-1,3,5-triazine in 20 ml of chlorobenzene isrefluxed. After concentration of the yellow solution by evaporation, andchromatographical purification of the residue, there is obtained acolourless oil which crystallises from an acetone/diethyl ether mixtureby the addition of hexane. The yield is 0.45 g (23.1% of theory) ofN-(2-difluoromethoxyphenylysulfonyl)-N'-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)-urea,m.p. 140°-141° C.

EXAMPLE 3 N-(2-Chlorophenyl-sulfonyl)-ethyl carbamate

6.65 ml of chloroformic acid ethyl ester are added to a mixture of 12.25g of 2-chlorophenylsulfonamide, 21.6 g of anhydrous potassium carbamateand 80 ml of anhydrous acetone at 20° to 25° C., and refluxing iscarried out for 2 hours. After cooling, the reaction mixture is taken upin 300 ml of ice-water and the mixture is filtered; the pH-value isadjusted to 2 with concentrated hydrochloric acid, and extraction isperformed with ethyl acetate. The combined organic phases are washedwith water, dried over sodium sulfate and concentrated by evaporation.The yield after crystallisation from an alcohol/water mixture is 14.9 gof N-(2-chlorophenylsulfonyl)-ethyl carbamate, m.p. 150°-152° C.

EXAMPLE 4N-(2-Methoxycarbonylphenyl-sulfonyl)-N'-(4-difluoromethoxy-6-methyl-pyrimidin-2-yl)-urea

A solution of 2.73 g of N-(2-methoxycarbonylphenylsulfonyl)-methylcarbamate and 1.75 g of 2-amino-4-difluoromethoxy-6-methyl-pyrimidine in50 ml of absolute dioxane is refluxed for 24 hours. After the solventhas been evaporated off, the residue is dissolved in a 5% sodiumcarbonate solution, and the solution is filtered; the pH-value isadjusted to 2 by acidifying with concentrated hydrochloric acid, andextraction is performed with ethyl acetate. The combined organic phasesare dried over sodium sulfate, and the solvent is evaporated off to thusobtain 3.2 g ofN-(2-methoxycarbonylphenylsulfonyl)-N'-(4-difluoromethoxy-6-methyl-pyrimidin-2-yl)urea,m.p. 162°-164° C.

The following intermediates of the formula VIa are produced in ananalogous manner.

                                      TABLE 1                                     __________________________________________________________________________    Comp. No.                                                                           G               QT          Physical data                               __________________________________________________________________________     1    2-ClC.sub.6 H.sub.4                                                                           OC.sub.2 H.sub.5                                                                          m.p. 150-152° C.                      2    2-OCH.sub.35-OCH.sub.3C.sub.6 H.sub.3                                                         OC.sub.2 H.sub.5                                                                          m.p. 132-133° C.                      3    2-OCH.sub.35-OCH.sub.3C.sub.6 H.sub.3                                                         SCH.sub.3   m.p. 182° C.                                                           (decomp.)                                    4    2-OCHF.sub.2C.sub.6 H.sub.4                                                                   OCH.sub.3   m.p. 138-140° C.                      5    2-OCHF.sub.2C.sub.6 H.sub.4                                                                   OC.sub.2 H.sub.5                                                                          m.p. 107-111° C.                      6    2-OCHF.sub.2C.sub.6 H.sub.4                                                                   OC.sub.4 H.sub.9n                                                                         n.sub.D.sup.20 = 1.4958                      7    2-OCH.sub.3C.sub.6 H.sub.4                                                                    OCH.sub.3                                                8    2-ClC.sub.6 H.sub.4                                                                           OCH.sub.3                                                9    2-ClC.sub.6 H.sub.4                                                                           OCH.sub.2CHCH.sub.2                                     10    2-ClC.sub.6 H.sub.4                                                                           OCH.sub.2C.sub.6 H.sub.5                                11    2-ClC.sub.6 H.sub.4                                                                            OCH.sub.2CF.sub.3                                      12    2-ClC.sub.6 H.sub.4                                                                           OCH.sub.2CCl.sub.3                                      13    2-ClC.sub.6 H.sub.4                                                                           SCH.sub.3                                               14    2-COOCH.sub.3C.sub.6 H.sub.4                                                                  OCH.sub.3   m.p. 162-164° C.                     15    2-NO.sub.2C.sub.6 H.sub.4                                                                     OCH.sub.3                                               16    2-[O(CH.sub.2).sub.2OCH.sub.3 ]C.sub.6 H.sub.4                                                OCH.sub.3                                               17    2-CF.sub.3C.sub.6 H.sub.4                                                                     OCH.sub.3                                               17    2-CH.sub.3C.sub.6 H.sub.4                                                                     OCH.sub.3                                               19                                                                                   ##STR7##       OCH.sub.3                                               20    2-COOCH.sub.3C.sub.6 H.sub.4                                                                  OC.sub.2 H.sub.5                                                                          m.p. 73-75° C.                       21    2-COOCH.sub.3C.sub.6 H.sub.4                                                                  OCH.sub.2CF.sub.3                                                                         m.p. 106-108° C.                     22    2-COOCH.sub.3C.sub.6 H.sub.4                                                                  OCH.sub.2C.sub.6 H.sub.5                                                                  m.p. 108° C.                         23    2-COOCH.sub.3C.sub.6 H.sub.4                                                                  OCH.sub.2CHCH.sub.2                                                                       m.p. 51-59° C.                       24    2-COOCH.sub.3 C.sub.6 H.sub.4                                                                 OCH.sub.2 CH.sub.2 OCH.sub.3                                                              n.sub.D.sup.21 : 1,5110                     25    2-COOCH.sub.3C.sub.6 H.sub.4                                                                  OC.sub.4 H.sub.9 (n)                                                                      m.p. 79-82° C.                       26    2-COOCH.sub.3C.sub.6 H.sub.4                                                                  OCH.sub.2 CCl.sub.2                                                                       n.sub.D.sup.21 : 1,528                      27    2-COOCH.sub.3C.sub.6 H.sub.4                                                                  OCH.sub.2 CH.sub.2 CN                                                                     m.p. 87°-89° C.               28    2-COOCH.sub.3C.sub.6 H.sub.4                                                                  SCH.sub.3   m.p. 133-4° C.                       29                                                                                   ##STR8##       OCH.sub.3                                               30    2-OCH.sub.2 CH.sub.2 ClC.sub.6 H.sub.4                                                        OCH.sub.3                                               __________________________________________________________________________

What is claimed is:
 1. A sulfonylcarbamate of the general formula VIa

    G--SO.sub.2 --NH--CO--Q--T                                 (VIa)

wherein Q is oxygen or sulfur, T is C₁ -C₄ -alkyl, C₁ -C₄ -haloalkyl, C₁-C₃ -cyanoalkyl, C₂ -C₅ -alkenyl, benzyl, or alkoxyalkyl oralkylthioalkyl having a total of at most 5 carbon atoms, and G is aradical of the formula ##STR9## wherein R₁ is hydrogen, C₁ -C₄ -alkyl,halogen, nitro, cyano, --NH₂, --S(O)_(n) -C₁ -C₄ -alkyl, --SO₂ -C₁ -C₄-alkoxy, --SO₂ -di-C₁ -C₄ -alkylamino, --CHO, --CONH₂, --D-C₃ -C₅-alkynyl, --CO-D-C₃ -C₅ -alkynyl, --D-C₁ -C₄ -alkyl, --D-C₃ -C₅-alkenyl, --CO-C₁ -C₄ -alkyl, --CO-D-C₁ -C₄ -alkyl or --CO-D-C₃ -C₅-alkenyl, n being one or two, and D is --O-- or --S--, R₂ is hydrogen,halogen, CF₃, NO₂, C₁ -C₄ -alkyl or C₁ -C₄ -alkoxy, R₃ is hydrogen, andR₄ is or is --O-C₁ -C₄ -alkyl, --CO-O-C₁ -C₄ -alkyl with the provisothat(a) the radical --Q-T is not ethoxy or butyloxy when G is theunsubstituted 2-thienyl radical, and the radical --Q-T is not methoxywhen G is the 2-methoxycarbonylphenyl radical.